This Application claims Priority from French Patent Application No. 97/5075 filed Dec. 1, 1997.
The present invention relates to the use of a dialkyldialkylammonium halide having a virucidal effect, via the systemic route, in the prevention and treatment of enveloped virus infections, and in particular in the prevention of new viral outbreaks capable of occurring following an organ transplant.
The virucidal action of quaternary ammoniums, and in particular of a dialkyldialkylammonium halide, such as didecyldimethylammonium chloride (Bardac(copyright)) on enveloped viruses is known.
These compounds are indeed used via the external route to destroy the viruses present on work surfaces, on linen or for example on equipment.
Moreover, compositions containing a dialkyldialkylammonium halide have proved particularly effective as virucidal agents when they are included in gloves (European Application 0,555,116), in order to avoid possible accidental infection of surgeons or of paramedical staff via a needle or surgical knife contaminated with an enveloped virus, such as the human immunodeficiency virus (HIV), the hepatitis B and C viruses, or the herpes group of viruses.
Immunodepression, which is induced in patients who have had an organ transplant in order to limit the risks of graft rejection, makes the occurrence of an infectious episode extremely frequent in these patients following their operations. This may be either a reactivation of a virus already present in the transplant recipient but in a dormant state, or a first infection when the virus is introduced by the transplanted organ a seronegative patient. The most frequent viral infections are due to the Herpes simplex, Epstein-Barr and cytomegalovirus viruses, the latter alone having an incidence of more than 50%. The activity of hepatitis B and C is also increased after transplant.
It can therefore be understood that it is desirable to have antiviral agents capable of preventing new viral outbreaks in transplant recipients or of treating these new outbreaks so as to avoid diffusion of the virus into the whole body.
The antivirals currently proposed in the treatment of viral infections are generally virustatic and nonvirucidal: they do not destroy the virus itself, but they reduce the production of virus by the infected cell, that is to say that their target is a replicating viral population. This mechanism involves, inside the infected cells, the inhibition of one of the viral replication steps: attachment, penetration, decapsidation, transcription, assembly, maturation and release of the newly-formed viral particles (virions) out of the cell.
By way of example, this is the mode of action of aciclovir or 9-[(2-hydroxyethoxy)methyl]guanine, which acts on viral replication by inhibiting the DNA polymerase of herpesviruses. It is also mode of action of the antivirals described in U.S. Pat. No. 4,902,720 for example tetraethylammonium chloride, which acts on the assembly of the constituents of the virus during its replication inside the cells.
In spite of their importance, virustatic antivirals do not constitute a completely satisfactory solution to the problem of viral infections. Indeed, by virtue of their inhibitory action on viral replication, they induce the emergence of resistant mutants which may lead, in the long run, to a phenomenon of tachyphylaxis.
The applicant has therefore set itself the objective of providing a composition capable of having virucidal activity when it is administered by the systemic route, so as to avoid the appearance of viral resistance. In particular, the applicant has set itself the objective of providing a virucidal composition capable of effectively preventing new viral outbreaks in organ transplant recipients.